Various tumor related diseases inflict man. Considerable research has been devoted to oncology and antitumor measures. Tumors are common in a variety of mammals and the prevention, control of the growth and regression of tumors in mammals is important to man. The term tumor refers to abnormal masses of new tissue growth which is discordant with the economy of the tissue of origin or of the host's body as a whole.
Tumors inflict mammals and man with a variety of disorders and conditions including various forms of cancer and resultant cancerous cachexia. Cancerous cachexia refers to the symptomatic discomfort that accompanies the infliction of a mammal with a tumor. These symptoms include weakened condition of the inflicted mammal as evidenced by, for example, weight loss. The seriousness of cancer is well known, e.g., cancer is second only to heart and vascular diseases as a cause of death in man.
While certain methods and chemical compositions have been developed which aid in inhibiting, remitting or controlling the growth of tumors further antitumor methods and chemical compositions are needed.
Immunomodulation is a developing segment of immunopharmacology. Immunomodulator compositions as the name implies, are compositions useful for modulating or regulating immunological functions in warm-blooded animals. Immunomodulators may be immunostimulants for building up immunities to or initiate healing of certain diseases and disorders or immunoinhibitors for preventing undesirable immuno reactions of the body to foreign materials. Immunomodulators have been found to be potentially useful for treating immune disease such as rheumatoid arthritis, neoplastic disease, infectious diseases, allergic reactions, autoimmune diseases, such as systemic lupus, erythematosus, and immunodeficiency diseases. Further such agents may be useful for immunotherapy of cancer or to prevent rejections in organ transplants, e.g. kidney or heart.
Various immunomodulator compositions have been discovered including muramylic acid dipeptide derivatives, levamisole, niridazole, oxysuran; flagyl, and others from the groups of interferons; interleukins; leukotrienes; and corticosteroids. Many of these compositions have been found, however, to have undesirable side effects and/or high toxicity. New immunomodulator compositions are therefore needed to provide a wider range of immunomodulator function for specific areas with a minimum of undesirable side effects.
Prevention of the growth of fungus and the infections and maladies caused by it to mammals and plants is also of importance to man. The presence of fungus may cause various diseases and infections in man including mycotic disease, e.g., pulmonary candidiasis and pulmonary blastomycosis. Certain yeastlike organisms, e.g., Cryptococcus neoformans, may cause serious infections of the central nervous system. More commonly known fungi infections in humans and mammals include ringworm, which are fungus infections of hair and nail areas, as well as resistant infections of the skin. Many other fungal infections inflict humans and mammals in the areas of skin, mucous membranes, intestinal tract, vaginal area and lungs.
Plants are also attacked by various fungi. Damage caused by fungus infection to agriculture amounts to billions of dollars annually. Various inorganic and organic fungistats and fungicides have been tried but with limited success. It is of course important for the fungistat or fungicide to kill the fungi but not the plant and to leave no toxic residue on the food of the plant. Various methods have been utilized to combat fungus infection in agriculture including foliage fungicide by which method plants are coated with a preventive weather-resistant fungicide. Seed treatment and soil treatment are methods which require fungicides which are safe for seeds and resist degradation by soil and soil microorganisms. Chemotherapeutants are fungicides which permeate the plant to protect new growth or eliminate infections which have already occurred within the plant. Agricultural fungistats and fungicides and their application must also meet very stringent requirements and regulations, which have been promulgated, for example, in the United States.
Considerable research and resources have been devoted to antitumor immunomodulatory and antifungal measures. While varius antitumor, immunomodulatory or antifungal agents and methods have been developed which aid in inhibiting tumors, immunomodulation and inhibiting the spread of fungus, respectively, additional methods and chemical agents are needed.
A potential source for useful organic compositions is marine plant and animal life and of particular interest are marine gorgonians. Gorgonacea are horny corals which may form fanlike or featherlike colonies of spreading branches. It has now been found that certain organic compounds derived from extracts of gorgonian Acalycigorgia sp. possess useful antitumor, immunomodulatory and antifungal acitivity.
Some compositions of interest have been previously isolated from marine gorgonian. These compositions named guaiazulene and linderazulene have been reported by Fusetani, N., Matsunaga, S., and Konosu, S. Experientia, 37, 680 (1981); Imre, S., Thomson, R. H., and Yalhi, B. Experientia, 37, 442 (1981); Li, M. K. W. and Scheuer, P. J. Tetrahedron Letters, 25, 587 (1984); Ibid., 25, 2109 (1984); Ibid., 25, 4707 (1984); Takeda, K., Minato, H., and Ishikawa, M., J. Chem. Soc., 2591 (1965); and Takeda, K. and Nagata, W. Chem. Pharm. Bull., 1, 164 (1953). These references do not disclose any antitumor, immunomodulatory or antifungal activity for these compositions. The entire disclosures of these references is hereby incorporated herein by reference. Thus, marine gorgonians and other marine life can be a source of useful raw materials for man.